title: Astrocyte-neuron lactate transport is required for long-term memory formation.
abstract: We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation.
authors.affiliation: Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Suzuki
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Stern
authors.forename: Ozlem
authors.initials: O
authors.lastname: Bozdagi
authors.forename: George W
authors.initials: GW
authors.lastname: Huntley
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Walker
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Magistretti
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Alberini
mesh_terms: D000818:Animals; D001089:Arabinose; D001253:Astrocytes / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D050113:Imino Furanoses; D019344:Lactic Acid / Q000378:metabolism*; D057567:Memory, Long-Term / Q000187:drug effects; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D013402:Sugar Alcohols / Q000494:pharmacology; D027981:Symporters / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D001089:Arabinose; D006003:Glycogen; D050113:Imino Furanoses; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D013402:Sugar Alcohols; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C498648:Slc16a4 protein, mouse; C058137:1,4-dideoxy-1,4-iminoarabinitol